The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective To analyze the safety and efficacy of laparoscopic radical resection of colorectal cancer for elderly patients over 70 years old. Methods From January 2014 to January 2017,a retrospective analysis of the patients with radical surgery for colorectal cancer in Department of General Surgery,Beijing Anzhen Hospital,Capital Medical University was performed. According to the patient′s age, the patients were divided into ≥70 years old group (68 cases) and＜70 years old group (84 cases). The preoperative clinical data of the two groups were analyzed. The surgeons strictly followed the standard lymph node cleaning and the principle of no tumor for colorectal cancer radical operation. The surgical conditions, pathology,short-term efficacy and the follow-up conditions of the two groups were compared. Statistical analysis was performed using SPSS 20. 0. The normal distribution of the data was expressed as Mean±SD,and the t-test was used for comparison between the group. The count data was compared using the χ2 test or the Fisher exact probability method. Results The operation was successfully completed in both groups. In the group of≥70 years old,2 cases were converted to open due to extensive adhesion of the abdominal cavity,no perioperative death. Compared with the＜70 years old group,≥70 years old group had more hypertension and coronary heart disease, respectively ( 38. 2%( 26/68 ) vs. 14. 3%( 12/84 )), and the difference was statistically significant ( P＜0. 05 ) . There was no significant difference in intraoperative blood loss and operation time between the two groups (P＞0. 05) . There was statistically significant difference in incidence of postoperative cardiovascular events between the groups (26. 4%(18/68) vs. 7. 14%(6/84)χ2＝ 6. 428, P＝0. 010) . However,there were no significant differences between the two groups in implications,rate of death and the time stayed in hospital. (P＞0. 05). Conclusion Laparoscopic radical resection for colorectal cancer patients over 70 years old is safe and feasible with strict indications and attention to perioperative management.

Chlamydia trachomatis (Ct) is the causative agent of bacterial sexually transmitted diseases (STDs) worldwide.The incidence of Ct infection has exceeded that of Neisseria gonorrhoeae,and becomes the highest in STDs in many countries.Ct infection can lead to urethritis,epididymitis,prostatitis and infertility in males,and cervicitis,endometritis,pelvic inflammatory disease,infertility in females,and neonatal conjunctivitis.Additionally,urogenital Ct infection is always ignored due to its concealed symptoms,leading to a long clinical course,recurrence or repeated infections.Furthermore,Ct infection can increase the risk of human immunodeficiency virus and human papilloma virus infections.Therefore,how to prevent and control the transmission of Ct has become one of the global public health issues.Currently,a growing body of researches have focused on the molecular epidemiological characteristics of Ct,which are aiming to identify the mutant strains,elaborate transmission dynamics,investigate the distribution of Ct serotypes in different populations,so as to provide molecular epidemiological evidence for the prevention and control of Ct infection.This review summarizes the epidemic status and research methods for molecular epidemiological characteristics of Ct,as well as application of Ct serotyping in clinical practice,providing references for the prevention,control and research of Ct infection.

Aim To investigate the hypoglycemic pathway of terpenes from Cornus officinalis(TCF) from three aspects of insulin dependence, α-glucosidase inhibition, insulin sensitizing.Methods Insulin-deficient diabetes mellitus(DM) model was induced by tail vein injection of streptozotocin(STZ) into SD rats at the dose of 50mg·kg-1 body weight.Rats were randomly divided into seven groups: control group(CON), model group(Model), metformin group(Met) 0.1g·kg-1, shenqi jiangtang granules(Shenqi) group 1.0 g·kg-1, three dose groups of TCF: 0.10, 0.05, 0.025 g·kg-1.Body weight and blood glucose were measured every week.After four weeks, glycosylated hemoglobin (HbA1c), glycosylated serum protein (GSP) were determined.Normal ICR mice were divided into seven groups: CON, Model, Met group 0.2g·kg-1, acarbose group(Acar) 0.1 g·kg-1, Shenqi group 1.5g·kg-1, three dose groups of TCF: 0.20g·kg-1;0.10g·kg-1;0.05 g·kg-1.After 10 days of administration, intraperitoneal injections of glucose and gavage starch tolerance tests were employed.Normal SD rats were divided into six groups: CON, rosiglitazone group 0.02 g·kg-1, glipizide group 0.02 g·kg-1, three dose groups of TCF: 0.10, 0.05, 0.025 g·kg-1.After seven days of administration, intraperitoneal glucose tolerance test(IPGTT) was employed and levels of insulin was determined.Results (1)High dose of TCF significantly reduced the level of HbA1c(P<0.05), GSP(P<0.05) on STZ model rats;(2)TCF significantly improved the glucose tolerance and gavage starch tolerance in ICR mice(P<0.05);(3) High dose of TCF significantly reduced the blood glucose and serum insulin level.Conclusions TCF has obvious effects on inhibiting glucose absorb and promoting the use of glucose.It is able to exert hypoglycemic effect through non-insulin dependent pathway, whereas, whether it has the effects of α-glucosidase inhibition and insulin sensitization should be further validated.

Adult ; Asian Continental Ancestry Group ; genetics ; Collagen Type I ; genetics ; Humans ; Mutation ; Osteogenesis Imperfecta ; genetics ; Pedigree ; Perinatal Death

The clinical electroencephalogram (EEG) monitoring systems based on personal computer system can not meet the requirements of portability and home usage. The epilepsy patients have to be monitored in hospital for an extended period of time, which imposes a heavy burden on hospitals. In the present study, we designed a portable 16-lead networked monitoring system based on the Android smart phone. The system uses some technologies including the active electrode, the WiFi wireless transmission, the multi-scale permutation entropy (MPE) algorithm, the back-propagation (BP) neural network algorithm, etc. Moreover, the software of Android mobile application can realize the processing and analysis of EEG data, the display of EEG waveform and the alarm of epileptic seizure. The system has been tested on the mobile phones with Android 2. 3 operating system or higher version and the results showed that this software ran accurately and steadily in the detection of epileptic seizure. In conclusion, this paper provides a portable and reliable solution for epileptic seizure monitoring in clinical and home applications.
Algorithms ; Cell Phone ; Electrocardiography ; Electroencephalography ; instrumentation ; Entropy ; Epilepsy ; diagnosis ; Humans ; Monitoring, Physiologic ; instrumentation ; Neural Networks (Computer) ; Software

To investigate the hypoglycemic effects of terpenes from Fructus Corni(TFC)on type 2 diabetes mellitus, the db/db diabetic mice were intragastrically administered with 25, 50, 100 mg/kg of TFC for 10 weeks. The fasting blood glucose, insulin(Ins), glycosylated serum protein(GSP), total cholesterol(TC)and triglyceride(TG)levels were determined. At weeks 8 and 10, intraperitoneal injections of glucose and gavage starch tolerance tests were performed, respectively. The db/db mice showed obvious obesity. Each dose of TFC could significantly reduce the body weight of db/db mice(P< 0. 05). After 4 weeks of administration, all doses of TFC significantly reduced the fasting blood glucose of db/db mice(P< 0. 05). The serum TC, TG levels were also significantly decreased in the TFC middle- and high-dose groups(P< 0. 05). In addition, middle- and high-dose of TFC could significantly reduce the level of GSP. Middle- and high-dose of TFC also significantly improve the glucose tolerance and gavage starch tolerance in db/db mice(P< 0. 05). These results suggest that TFC could improve diabetes-related symptoms via regulating glucose and lipids metabolism.

We amplified genes encoding UDP-glucose dehydrogenase, ecohasB from Escherichia coli and spyhasB from Streptococcus pyogenes. Both ecohasB and spyhasB were inserted into T7 expression vector pRX2 to construct recombinant plasmids pRXEB and pRXSB, and to express in E. coli BL21(DE3). After nickel column purification of UDP-glucose dehydrogenases, the enzymes were characterized. The optimum reaction condition of spyHasB was at 30 °C and pH 10. The specific activity reached 12.2 U/mg under optimum condition. The optimum reaction condition of ecoHasB was at 30 °C and pH 9. Its specific activity reached 5.55 U/mg under optimum condition. The pmuhasA gene encoding hyaluronic acid synthase was amplified from Pasteurella multocida and ligated with ecohasB and spyhasB to construct the coexpression vectors pBPAEB and pBPASB, respectively. The co-expression vectors were transformed into E. coli BW25113. Hyaluronic acid (HA) was produced by biotransformation and the conditions were optimized. When recombinant strains were used to produce hyaluronic acid, the higher the activity of UDP-glucose dehydrogenase was, the better its stability was, and the higher the HA production could reach. Under the optimal conditions, the yields of HA produced by pBPAEB/BW25113 and pBPASB/BW25113 in shake flasks were 1.52 and 1.70 g/L, respectively, and the production increased more than 2-3 folds as previously reported.
Biotransformation ; Escherichia coli ; enzymology ; Genetic Vectors ; Glucuronosyltransferase ; genetics ; Hyaluronan Synthases ; Hyaluronic Acid ; metabolism ; Pasteurella multocida ; enzymology ; Streptococcus pyogenes ; enzymology ; Uridine Diphosphate Glucose Dehydrogenase ; metabolism